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Biomedical subjects

R Hunt

Publications and source records attributed to R Hunt.

At least 55 records · Page 3Linked to original sources

Structural requirements for addition of O-linked carbohydrate to recombinant erythropoietin.

To define the structural requirements for addition of O-linked glycosylation in vivo, recombinant erythropoietin (rEPO) variants were constructed. Thirty-three independent Ser or Thr substitutions were constructed and examined to see which were subject to O-linked carbohydrate addition. Variants with Thr mutations at positions 123 and 125, but not elsewhere, contained additional carbohydrate, which suggests that several positions around the existing O-linked glycosylation site (Ser126), but not elsewhere, contain the necessary information for O-linked carbohydrate addition. Two forms of the Thr125 variant were identified. One form was glycosylated only at residue 125, and a second form was glycosylated at both Thr125 and Ser126, the normal O-glycosylation site. We have also found that glycosylation is less efficient when rEPO is improperly folded and that prolines at -1 and +1 relative to the O-glycosylation site enhance glycosylation.

Amino Acid Sequence↗

Method for simultaneous isolation and quantitation of platelet activating factor and multiple arachidonate metabolites from small samples: analysis of effects of Staphylococcus aureus enterotoxin B in mice.

A novel method has been developed for the extraction and simultaneous separation and quantitation of key arachidonate metabolites and platelet activating factor (PAF) from plasma samples of limited size. Aqueous solutions of these metabolites were added onto a solid phase C-18 cartridge and arachidonate metabolites and PAF were eluted, successively, with acetonitrile-methanol (85:15, v/v), followed by 100% methanol. Arachidonate metabolites (first eluate) were fractionated by C-18 reverse-phase high-performance liquid chromatography using a program designed for the resolution of 31 arachidonate metabolites (3-min separation). The fractions were collected and assayed by radioimmunoassay or radiography, if radioactively labeled. Two internal standards were added to each sample, 15-hydroxyeicosadienoic acid (detected at 235 nm) to determine gradient shifts and [1-14C]eicosatrienoic acid to estimate the recoveries of arachidonate metabolites at any stage of the process. This method was developed to answer specific questions concerning the mode of action of Staphylococcus aureus enterotoxin B (SEB). Plasma samples from mice challenged with SEB were analyzed and major differences were seen in 5-lipoxygenase metabolites. Low doses of SEB vs saline stimulated 5-hydroxyeicosatetraenoic acid production, while high doses of SEB stimulated leukotriene D4 production.

Animals↗

Receiver operating characteristic evaluation of computer display of adult portable chest radiographs.

RATIONALE AND OBJECTIVES: The suitability of using an image console monitor for interpretation of adult portable chest radiographs was evaluated with receiver operating characteristic (ROC) analysis and subjective techniques. METHODS: Radiologists read 80 chest images, once on a display monitor and once on computed radiography film, for the presence or absence of pneumothorax or atelectasis. Judgments of correct or incorrect positions of tubes and lines were reported, and total viewing time was recorded. RESULTS: A statistically significant difference was found in favor of monitor reading for detection of pneumothoraces. Atelectasis detection also was higher with monitor reading, but the difference did not reach statistical significance. Tube/line judgments were equivalent for both modes. Total viewing time was approximately 1 minute longer per image with the monitor. CONCLUSIONS: Viewing computed radiography images on a workstation monitor does not seem to affect diagnostic accuracy compared with film viewing. Preset image defaults tailored to the individual radiologist could decrease total viewing time to acceptable levels.

Adult↗

Helicobacter pylori infection in adolescents with eating disorders and dyspeptic symptoms.

The potential role of Helicobacter pylori infection of the antrum as a cause of symptoms of dyspepsia in patients with eating disorders was evaluated with an assay to detect H. pylori-specific IgG in serum. H. pylori-specific optical-density readings were comparable for adolescents with eating disorders (0.133 +/- 0.063, mean +/- SD) and for two comparison groups, and were lower than readings for children with documented H. pylori infection. Symptoms referable to the gastrointestinal tract did not correlate with H. pylori status in the teenagers with eating disorders.

Adolescent↗

Trends in the terminal care of cancer patients: South Australia, 1981-1990.

BACKGROUND: The increasing numbers of cancer patients, the high costs of terminal care, and the development of palliative care services have led to a growing interest in patterns of terminal cancer care. These patterns are relevant to the formulation and evaluation of health services policy. AIMS: To investigate trends in the place of death of South Australian cancer patients between 1981 and 1990, and to examine associations of socio-demographic and clinical variables with the place of death. METHODS: Data relating to 2715 deaths attributed to cancer in 1990 were extracted from the Central Cancer Registry. To assess trends, these data were directly standardised to the age-sex distribution of cancer deaths in 1981 and 1985 which were investigated in a previous study. Unconditional logistic regression was used to investigate predictors of place of death. RESULTS: The proportion of deaths which occurred in major metropolitan public hospitals decreased from 40% in 1981 to 28% in 1990. Conversely, the proportion which occurred in hospice units increased from 5% to 20% over the same period. There was a decline in the proportion of deaths which occurred in private hospitals, but there was no significant change in the proportion which occurred in country hospitals or nursing homes. The proportion of deaths at home remained around 14%. Associated with place of death were age, sex, type of malignancy, survival time from diagnosis to death, Aboriginality, and area of residence. Further research to assess the clinical appropriateness of terminal care patterns is suggested.

Aged↗

Armadillos (Dasypus novemcinctus) as a model to test antileprosy vaccines; a preliminary report.

The efficacy of two candidate leprosy vaccines, BCG and a mixture of BCG and killed Mycobacterium leprae, was tested in 62 armadillos caught in the wild. The abilities of the vaccines to convert lepromin-negative armadillos to a positive reaction were compared with a group of control animals. Both vaccines upgraded subsequent lepromin skin-test histopathology. The conversion results parallel the protection values obtained in some BCG vaccine trials against leprosy in humans. Before conducting expensive human trials with new antileprosy vaccines, it would be worthwhile first to evaluate them in the armadillo model.

Animals↗

Therapeutic role of dietary fibre.

The current status of dietary fibre and fibre supplements in health and disease is reported, and the components of dietary fibre and its respective mechanical and metabolic effects with emphasis on its therapeutic potential are reviewed. Practical management guidelines are provided to help physicians encourage patients identified as having fibre deficiency to increase dietary fibre intake to the recommended level.

Adult↗

Increased lymphatic pumping ability in pregnant ewes.

OBJECTIVE: Daily the lymphatic system returns several liters of fluid to the systemic circulation. Unlike blood, lymph is pumped against a pressure gradient. Because vessels in the systemic circulation are hyporesponsive to vasoconstrictor hormones during pregnancy, we decided to assess whether lymphatic pumping ability was decreased during pregnancy. STUDY DESIGN: Ten pregnant ewes were chronically catheterized in the left thoracic duct and jugular vein. Four days after surgery thoracic duct pumping ability was determined by measuring the lymph flow rate as a function of outflow pressure by varying the height at which lymph flow drains in an open-flow system. RESULTS: Lymph flow was plotted against outflow pressure, and the value at which lymph flow decreases is defined as the "breaking point." The outflow pressure at which lymph flow equals zero is the "stopflow" pressure; this value defines the pumping ability. The pregnant ewes had a breaking point of -1 +/- 2.7 versus 14.4 +/- 3.0 mm Hg (mean +/- SD) for the nonpregnant sheep. Stopflow pressures were 62 +/- 7.3 versus 23.9 +/- 4.7 mm Hg (mean +/- SD) for the nonpregnant ewes (p < 0.05). CONCLUSIONS: The ability of the lymphatic system to generate pressure is increased during pregnancy, but the breaking point is diminished. Alterations of lymphatic pumping ability could explain fluid retention under pathophysiologic conditions.

Animals↗

Glucose turnover and its regulation during intense exercise and recovery in normal male subjects.

Intense exercise to exhaustion is expected to be associated with rapid and large changes in glucose production (Ra) and utilization (Rd). To quantify these, and to determine their mechanisms and those of the prolonged postexercise hyperglycemia, we measured circulating metabolic regulators and glucose kinetics, the latter by the method of enriched tracer [3-3H] glucose infusion during exercise. Eighteen fit, lean young male subjects exercised to exhaustion at 80% of maximal workload (approximately 100% VO2max) on a cycle ergometer. Plasma glucose was 4.90 +/- 0.08 mM/L at rest, increased during exercise, then abruptly to 6.91 +/- 0.40 mM/L at 4 min recovery then gradually declined. Plasma insulin was constant during exercise, then doubled to 162 +/- 28 pmol/l until 20 min recovery, before declining. Plasma glucagon increased by 71 +/- 11 pg/mL. Plasma norepinephrine increased 18-fold and epinephrine 14-fold, both declining by 20 min recovery. Ra increased 7-fold by exhaustion to 13.0 +/- 1.18 mg/kg/min, then decreased to 2.43 +/- 0.24 mg/kg/min by 9 min, then to about 2 mg/kg/min the rest of recovery. Rd rose 3-fold (6.61 +/- 0.70 mg/kg/min), and remained lower than Ra to 7 min recovery, but thereafter declined more slowly. Thus, the rapid and extremely large increase in Ra was not matched by the increment in Rd during exercise and early recovery. We suggest that unlike in exercise of lesser intensity, the major mediators of both the increase in Ra and the restraint of the increase in Rd are the catecholamines. The post exercise hyperglycemia and hyperinsulinemia are appropriate to muscle glycogen repletion.

Adult↗

Detection of breast abnormalities on teleradiology transmitted mammograms.

The authors conducted an observer performance study to compare breast lesion detection of conventional mammography (CM) with teleradiology (TE) transmitted mammograms. One hundred four abnormal, single-projection mammographic images were transmitted by teleradiology. Abnormalities included 11 cases with skin thickening or retraction, 48 cases with microcalcifications, and 52 with parenchymal masses. The CM and TE images were reviewed by four mammographers who indicated the type and location of abnormalities and a level of confidence for their diagnostic decisions. For each of three detection tasks--skin and nipple abnormalities, microcalcifications, and masses--receiver operating characteristic curve analysis was performed for individual readers and all readers as a group. For detecting skin and nipple abnormalities, readers performed significantly better with CM than with TE (z = 2.05, P = less than 0.04). However, no significant differences were found among readers for detection of either microcalcifications or masses. Further improvements in hardware and imaging parameters may improve detection of soft tissue abnormalities. Further evaluation is necessary to determine whether teleradiology might be applicable to breast cancer screening.

Breast Neoplasms↗

Staphylococcus aureus enterotoxin B challenge of monkeys: correlation of plasma levels of arachidonic acid cascade products with occurrence of illness.

Arachidonic acid cascade products have been shown to be increased in vitro in Staphylococcus aureus enterotoxin B (SEB)-treated epithelial cell cultures in our laboratory. In order to confirm that these products were clinically related to SEB intoxication, monkeys were administered SEB by nasogastric intubation. It caused emesis in five of six monkeys (less than 4 h), and the sixth monkey showed signs of mild illness. The monkeys which vomited continued to display signs of gastrointestinal illness beyond 8 h but were without any apparent signs of illness by 24 h. Blood samples were collected prior to SEB administration, upon first indication of illness, and at twice that time interval. One week prior to SEB treatment, the same monkeys were administered saline by nasogastric intubation and in every way handled similarly in order to serve as their own controls. Blood samples were taken from the control animals at 0, 4, and 8 h. The plasma concentrations of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE) did not vary significantly throughout the 8-h experiment for saline-treated controls, nor did they differ from the concentrations found in the plasma of monkeys just before administration of SEB. When the SEB-treated monkeys showed the first indication of illness (less than 4 h), the mean of the concentration in plasma of PGE2 increased 1.44-fold, that of LTB4 increased 2.23-fold, and that of 5-HETE was essentially unchanged. At twice the time interval of the first display of illness (less than 8 h), PGE2 was still elevated (1.48-fold), LTB4 had decreased slightly to 1.66-fold, and 5-HETE had soared (3,45-fold), suggesting a divergence in the enzymatic utilization of the parent compound of the latter two metabolites, 5-hydroperoxyeicosatetraenoic acid. These studies suggest that arachidonic acid cascade metabolites were a consequence of SEB intoxication and may provide a logical site for metabolic interference in SEB-induced toxicity.

Animals↗

Roger Hunt negotiates a new academic affiliation. Interview by Donald E.L. Johnson.

Roger Hunt is president and chief executive officer of Lutheran General Hospital, Park Ridge, Illinois. The north suburban Chicago hospital recently signed a letter of intent to shift its primary academic affiliation to the University of Chicago Medical School, which is on the south side of the city. More than 20 miles and more than an hour of freeway and city street driving separate the organizations. Health Care Strategic Management's editor and publisher, Donald E.L. Johnson, talked with Roger Hunt about Lutheran General's strategy for selecting a medical school and creating a teaching program that works for all concerned.

Academic Medical Centers↗